Role of monocytes in endothelial glycocalyx shedding during Puumala orthohantavirus infection

Abstract

AbstractVascular leakage characterizes Puumala orthohantavirus (PUUV)-caused hemorrhagic fever with renal syndrome (HFRS). Disruption in the endothelial glycocalyx layer, which protects blood vessels from increased vascular leakage into tissues, may contribute to disease severity during acute PUUV-HFRS. Recent evidence suggests that increased heparanase (HPSE) activity could play a role in glycocalyx degradation. Additionally, dynamic changes in monocyte populations, especially a decrease in endothelium “patrolling” CD14+CD16+nonclassical monocytes (NCMs) are observed in acute PUUV-HFRS. To investigate HPSE expression levels in different monocyte subsets and their relationship to the numbers of circulating endothelial cells (CECs) as marker of glycocalyx degradation during PUUV-HFRS, we analyzed patient peripheral blood mononuclear cells collected at acute and recovery stages of the disease by flow cytometry. CECs were significantly increased in acute PUUV-HFRS patients, and gradually decreased towards the postacute and recovery phases. Moreover, we identified significant correlations between CECs, the frequencies of different monocyte subsets and their HPSE expression, and clinical parameters. The decrease in HPSE expressing NCMs correlated with plasma HPSE levels, indicating a potential role for monocytes in modulating endothelial glycocalyx shedding. Furthermore, co-culture experiments suggested PUUV-infected endothelial cells (ECs) as regulators of monocyte HPSE expression. The study enhances understanding of EC and monocyte dynamics during PUUV-HFRS, providing insights into immune responses and potential vascular complications. Subtle variations in monocyte subsets emphasize their possible variable roles in disease progression and changes throughout the disease course. Overall, the study contributes to unraveling the complex interactions between viral infections, immune responses, and vascular dynamics, guiding future investigations and interventions in PUUV-HFRS-associated vascular complications and glycocalyx shedding in the kidneys.